Population Genetics Flashcards
Only 10% of human DNA codes for genes, and only 1% are
Exons
The promoter upstream of the 5’ terminus regulates the initiation of DNA transcription into single stranded
mRNA
How many codons specify translation into the 20 amino acids of the protein?
64 (three are stop codons)
Non-corrected transcription errors make
Mutant (abnormal) proteins
Humans have 2 sets of homologous chromosomes (diploid). Thus, there are 2 copies of each
Gene (allele)
If both alleles are the same, the individual is said to be a
Homozygote
If the two alleles are different, the individual is a
Heterozygote
At a population level, there may be multiple alleles at each locus. These allelic variations can be expressed in different proportions in the
Population
A single nucleotide change (SNP) or insertion/deletion (Indel) of a nucleotide that has been transmitted throughout generations
Polymorphisms
Polymorphisms are a single nucleotide change (SNP) or insertion/deletion (Indel) of a nucleotide that has been transmitted throughout generations reaching a frequency of
1 in 100 in the population
The frequency of “Phenotypic Traits” caused by an allele within a loci can vary among
Populations
Remember that many phenotypic manifestations defy a simple Phenotype-Genotype Mendelian categorization and must be modeled using
Gene interactions together with environmental exposures
What are the assumptions needed for assuming we have a population in Hardy-Weinburg (H-W) equilibrium?
- ) Random mating
- ) No changes due to migration
- ) No large fluctuations in allele frequency (i.e. genetic drift)
- ) No positive or negative selection
Means that all genotypes reproduce equally well
No positive or negative selection
In H-W equilibrium, we can have no large fluctuations in allele frequency caused by the effects of: natural selection, genetic drift, founder effect, bottleneck, or
Inbreeding
Selection against homozygous individuals and advantage for heterozygotes in a given environment
Ex: the ability of sickle cell heterozygotes to fight off malaria
Natural selection
Variation in the relative frequency of different genotypes in a small population, owing to the chance disappearance of particular genes as individuals die or do not reproduce
Genetic Drift
The frequency of Ellis-van Creveld syndrome in PA is greater than expected from random distribution of alleles, this is due to
Genetic drift
Characterized by short stature, polydactyly, and heart disease
Ellis-van Creveld syndrome
A deleterious rare allele seen at a relatively high frequency in a small/isolated population derived from 1 ancestor
Ex: Huntington’s Disease in Maracaibo
Founder effect
High frequency of an allele in a population that underwent historical population constrictions
-Ex: the frequency of Gaucher, Tay-Sachs, Torsion dystonia in the Ashkenazi Jewish population
Bottleneck effect
Consanguinous mating (between relatives) that increases the amount of homoxygotes
Inbreeding
Subpopulation stratification by selective mating (marriage arrangements) increases the rate of homozygotes and the probability of distinct phenotypic traits in some
Populations
Occurs in up to 60% of people in some geographic regions
Endogamy (marrying only within limits of tribe/community)
What leads to genetic variations among populations?
Natural selection, Genetic Drift, Founder effect, Bottleneck effect, and Inbreeding
Says that the chance that a genetic disorder will occur depends on the observed frequency of the disease in the population
Hardy-Weinberg principle
Allows us to calculate the frequencies for 2 alleles (A and B) in a population in equilibrium (p + q = 1)
-Where p = frequency of A and q = frequency of B
H-W calculation
In the H-W calculation, what are the types of people in the population?
AA = p^2
BB= q^2
AB = 2pq
What is the H-W equation?
p^2 + 2pq + q^2 = 1
In the H-W equation, the total number of allele A in the population is
A = p^2 + 2p
In the H-W equation, the total number of allele B in the population is
B = q^2 + 2q
For X-linked recessive traits, males are
Hemizygous for A or B (i.e AY or BY)
For X-linked recessive traits, females can still be
AA, BB, or AB
When talking about H-W and a disease, what is the:
- ) frequency of the normal allele?
- ) Frequency of the disease producing allele?
- ) p
2. ) q
If the disease frequency is 1/2500, what is q^2? what about q?
q^2 = 1/2500
q = 1/50
What portion of alleles are shared by 1st cousins?
1/8
What is the coefficient of inbreeding (f) for 1st cousins?
(1/8) x (1/8) x 4 possible alleles for that loci = 1/16
When 1st degree relatives mate (father-daughter, brother-sister), what is the risk for a significant phenotypic abnormality?
40%
When dealing with incest, what is the percentage of children born with
- ) AR disorders
- ) malformations/sudden infant death syndrome
- ) severe intellectual impairment
- ) mild intellectual impairment
- ) 12%
- ) 18%
- ) 12%
- ) 14%
When second degree relatives (i.e. uncle and niece or half siblings) have children, the overall risk for congenital anomalies lies between the risk for 1st cousins and incest. It is about
6%-18%
When 1st cousins procreate, since they are sharing 1/8 of their genes, what is the risk for
- ) mental retardation
- ) infant mortality
- ) 3-6%
2. ) 4.4%
What is the empiric risk in the general population for
- ) AD disorders
- ) AR disorders
- ) X-Linked disorders
- ) Chromosomal disorders
- ) Congenital malformations
- ) 1%
- ) 0.25%
- ) 0.2%
- ) 1%
- ) 3-5%
Increases the risk for multi-factorial and recessive diseases
Consanguinity
Autosomal dominant disorder affecting 1 in 20,000 individuals in the general population. Classical example of age dependent penetrance of a devastating neurologic deterioration disorder.
Huntington’s disease
Very few individuals manifest signs of huntingtons in childhood, while 100% have symptoms by age
80
Huntington’s inevitably leads to death with loss of the basal ganglia of the brain, specifically the
Caudate Nucleus
One of the first disorders subjected to “ large family genome polymorphic markers scan and positional cloning ” making in 1981 for linkage-based diagnosis by haplotype analysis in pre-symptomatic patients.
Huntington’s
An X-linked recessive disease caused by an F-VIII gene pathogenic mutation (most common in intron 22-A and intron-1 inversion)
Hemophilia A
What is the incidence of hemophilia A in
- ) Males
- ) Females
- ) 1/4000
2. ) rare
10-15% of hemophilia A occurs
De novo
What is the penetrance of hemophilia A in
- ) Males
- ) Females
- ) 100%
2. ) 10%
Severe deficiency in the factor-VIII clotting activity assay is associated with spontaneous joint or deep tissue
Bleeding
Associated with prolonged bleeding after tooth extractions, surgery, or injuries
Moderate/mild deficiency of factor V-III clotting activity
What are the four Bayesian Terminologies?
- ) Prior probability
- ) Conditional probability
- ) Joint probability
- Posterior probability
Mendelian probabilities that the parent is or is not a carrier
Prior probability
Information gathered based on whether siblings are or are not affected
Conditional probability
The product of prior and conditional probabilities
Joint probability
The ratio of the joint probability of one outcome to the sum of all joint probabilities
Posterior probability
When 2 events are independent, p1 and p2, the probability for both occuring together is
p1 x p2
When one event can happen in 3-ways with individual probabilities of p1, p2, and p3, then the overall probability is
p1 + p2 + p3
The probability that in this scenario the event will happen by way of #1 is then
p1 / (p1 + p2 + p3)
Relates to the quantitative study of the distribution of genetic variation in populations and how they are maintained or changed over time
Population genetics
Disease frequencies often vary based on
Ethnicity
When we need to use H-W, knowing the disease frequency will give us
q^2
Around the globe, polymorphisms reach a frequency of
1 in 100
